A model of the GABAA receptor-chloride ion channel macromolecular complex (others could be proposed). A heterooligomeric glycoprotein, the complex consists of five or more membrane-spanning subunits. Multiple forms of , , and subunits are arranged in different pentameric combinations so that GABAA receptors exhibit molecular heterogeneity. GABA appears to interact with or subunits triggering chloride channel opening with resulting membrane hyperpolarization. Binding of benzodiazepines to subunits or to an area of the unit influenced by the unit facilitates the process of channel opening but does not directly initiate chloride current. (Modified and reproduced, with permission,
Drug administration and pharmacology of phenobarbital
Drug Administration Laboratory of PharmacologyDepartment of Pharmacology and Therapeutics Faculty of Medicine Diponegoro University 2012
0 Phenobarbital 1sDrugsused in the prophylaxisof epileptic seizures • Barbiturate drug, trade name O H Luminal O C 3 H H N N C CH • MainlyC Anticonvulsant as C H5 2 2 5 O C O C O C • Hypnotic effect, Sedative effect, C N N N C • Bioavailability after proper H H O H administration = 95% O • Metabolism= Hepatic Phenobarbital (Cytochrome P450) E P henytoin thosuximide • Half-life= 53-118 hours C 2 H • Excretion= Renal and Fecal HC C 2 H NH2 H2C NH2 HC NH2 C 2 H C C 2 H
Clinical Use• Phenobarbital is useful in the treatment of partial seizures and generalized tonic-clonic seizures, although the drug is often tried for virtually every seizure type, especially when attacks are difficult to control• Depresses neurons activities via Reticular Formation, Induces sleep (Sedative, Hypnotics, and Anesthetics)
GABA-mediated chloride ion channelfrom Zorumski CF, Isenberg KE: Insights into the structure and function of GABA receptors: Ionchannels and psychiatry. Am J Psychiatry 1991;148:162.)
Pharmacokinetics• The rates of oral absorption of sedative- hypnotics differ depending on a number of factors, including lipophilicity.• Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration.
Pharmacodynamics• Benzodiazepines and phenobarbital augment the activation of the GABAA receptor by physiologically released amounts of GABA.• Elongates the GABA-mediated Chloride Ion Channel Opening.• Elongates GABA and Glycine Inhibitory Effect• Chloride influx is increased, counteracting depolarization.• Depresses the CNS via Reticular Formation.• Induces sleep (Sedative, Hypnotics, and Anesthetics)